Abstract
Influenza virus infections pre-dispose an individual to secondary pneumococcal infections, which represent a serious public health concern. Matching influenza vaccination was demonstrated helpful in preventing postinfluenza bacterial infections and associated illnesses in humans. Yet, the impact of influenza hemagglutinin (HA)-specific immunity alone in this dual-infection scenario remains elusive. In the present study, we assessed the protective effect of neutralizing and non-neutralizing anti-hemagglutinin immunity in a BALB/c influenza-pneumococcus superinfection model. Our immunogens were insect cell-expressed hemagglutinin-Gag virus-like particles that had been differentially-treated for the inactivation of bioprocess-related baculovirus impurities. We evaluated the potential of several formulations to restrain the primary infection with vaccine-matched or -mismatched influenza strains and secondary bacterial replication. In addition, we investigated the effect of anti-HA immunity on the interferon status in mouse lungs prior to bacterial challenge. In our experimental setup, neutralizing anti-HA immunity provided significant but incomplete protection from postinfluenza bacterial superinfection, despite effective control of viral replication. In view of this, it was surprising to observe a survival advantage with non-neutralizing adaptive immunity when using a heterologous viral challenge strain. Our findings suggest that both neutralizing and non-neutralizing anti-HA immunity can reduce disease and mortality caused by postinfluenza pneumococcal infections.
Highlights
A leading cause of the mortality observed during both seasonal and pandemic influenza outbreaks can be attributed to secondary respiratory infections with bacteria, such as Streptococcus pneumoniae (S. pneumoniae, pneumococcus) [1]
We used a virus‐like particle (VLP)‐based immunogen due to several reasons: (1) VLPs enabled us to investigate immunity conferred by a single influenza antigen animals were sacrificed for the assessment of innate immune activation at the vaccination site by and (2) five
VLPs allow for the presentation of the HA in its native conformation in particulate and highly analysis of type I/II interferon expression in peritoneal washes
Summary
A leading cause of the mortality observed during both seasonal and pandemic influenza outbreaks can be attributed to secondary respiratory infections with bacteria, such as Streptococcus pneumoniae (S. pneumoniae, pneumococcus) [1]. There is strong evidence that virus-mediated activation of innate immunity plays a decisive role in rendering an influenza-infected individual less capable of mounting a proper immune response towards a secondary bacterial invader [5,6,7,8,9]. In this regard, expression of the innate cytokines type I (α/β) and type II (γ) interferon (IFN) in response to viral infection can attenuate the phagocytic function of tissue-resident alveolar macrophages (AMs) [10,11] or impair the recruitment of neutrophils [12] and natural killer (NK)
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